Mechanisms of aging in the tissue progenitor cells and tissue regeneration

• Project/Area Number: 16KT0125
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Neo-Gerontology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Matsuda Yoko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (20363187)
• Co-Investigator(Kenkyū-buntansha): 松下 晃 日本医科大学, 医学部, 助教 (70449263) ; 石渡 俊行 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (90203041)
• Project Period (FY): 2016-07-19 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 老化 / テロメア / 膵癌 / 組織前駆細胞 / 加齢 / 前駆細胞 / SOX9 / 一塩基多型 / 膵臓 / 幹細胞 / 癌 / 糖尿病 / 病理 / 解剖 / 発がん

Outline of Final Research Achievements

Telomeres are regions with tandem repeats of nucleotide sequences (TTAGGG) at each end of a chromatid in eukaryotes, and plays a key role in preventing chromosomal instability. In this study, we analyzed telomere length in exocrine cells of the human pancreas with and without cancer. The telomere length was the longest in ducts, followed by centroacinar cells, and acinar cells. Telomere length in duct, centroacinar and acinar cells decreased with age. The rate of decline in telomere length due to age was greater in duct cells, followed by centroacinar cells, and acinar cells. The length of telomeres in the duct and centroacinar cells of pancreatic cancer cases was shorter than that in the cells of the cases without cancers. In conclusion, critical telomere dysfunction in the centroacinar-acinar region is possibly due to high annual telomere attrition, which leads to chromosomal instability and carcinogenesis in the pancreas.

Academic Significance and Societal Importance of the Research Achievements

本研究により、組織前駆細胞と発がんとの関連が明らかとなった。これにより、がんの予防、診断、治療法開発につながる基礎的情報が入手できた。また、加齢による膵臓の変化が明らかになったことから、高齢者の発がんや膵臓の機能異常の機序の解明に繋がる可能性がある。膵臓だけでなく、他の臓器にも応用可能であり、その波及効果は広いと考える。

Research Products

• [Journal Article] The stem cell-specific intermediate filament nestin missense variation p.A1199P is associated with pancreatic cancer (2019)
  • Author(s): Matsuda Yoko、Tanaka Masashi、Sawabe Motoji、Mori Seijiro、Muramatsu Masaaki、Naka Mieno Makiko、Ishiwata Toshiyuki、Arai Tomio
  • Journal Title: Oncology Letters Volume: 17 Pages: 4647-54
  • DOI: 10.3892/ol.2019.10106
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathological characteristics of distant metastases of adenocarcinoma, squamous cell carcinoma and urothelial carcinoma : An autopsy study of older Japanese patients. (2018)
  • Author(s): Matsuda Y, Seki A, Nonaka K, Kakizaki M, Wang T, Aida J, Ishikawa N, Nakano Y, Kaneda D, Takata T, Takahashi-Fujigasaki J, Murayama S, Takubo K, Ishiwata T, Sawabe M, Arai T.
  • Journal Title: Geriatr Gerontol Int. Volume: 18 Issue: 2 Pages: 211-215
  • DOI: 10.1111/ggi.13165
  • Peer Reviewed / Open Access
• [Journal Article] Telomere length determined by the fluorescence in?situ hybridisation distinguishes malignant and benign cells in cytological specimens (2018)
  • Author(s): Matsuda Y.、Suzuki A.、Esaka S.、Hamashima Y.、Imaizumi M.、Kinoshita M.、Shirahata H.、Kiso Y.、Kojima H.、Matsukawa M.、Fujii Y.、Ishikawa N.、Aida J.、Takubo K.、Ishiwata T.、Nishimura M.、Arai T.
  • Journal Title: Cytopathology Volume: 29 Issue: 3 Pages: 262-266
  • DOI: 10.1111/cyt.12535
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Abnormal immunolabelling of SMAD 4 in cell block specimens to distinguish malignant and benign pancreatic cells (2018)
  • Author(s): Matsuda Yoko、Esaka Shikine、Suzuki Akemi、Hamashima Yuri、Imaizumi Masayuki、Matsukawa Miho、Fujii Yuko、Aida Junko、Takubo Kaiyo、Ishiwata Toshiyuki、Nishimura Makoto、Arai Tomio
  • Journal Title: Cytopathology Volume: 30 Issue: 2 Pages: 201-208
  • DOI: 10.1111/cyt.12653
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Relationship between pancreatic intraepithelial neoplasias, pancreatic ductal adenocarcinomas, and single nucleotide polymorphisms in autopsied elderly patients (2017)
  • Author(s): Matsuda Yoko、Tanaka Masashi、Sawabe Motoji、Mori Seijiro、Muramatsu Masaaki、Mieno Makiko Naka、Furukawa Toru、Arai Tomio
  • Journal Title: Genes, Chromosomes and Cancer Volume: 57 Issue: 1 Pages: 12-18
  • DOI: 10.1002/gcc.22479
  • Peer Reviewed / Open Access
• [Journal Article] The Prevalence and Clinicopathological Characteristics of High-Grade Pancreatic Intraepithelial Neoplasia: Autopsy Study Evaluating the Entire Pancreatic Parenchyma. (2017)
  • Author(s): 1.Matsuda Y, Furukawa T, Yachida S, Nishimura M, Seki A, Nonaka K, Aida J, Takubo K, Ishiwata T, Kimura W, Arai T, Mino-Kenudson M.
  • Journal Title: Ｐａｎｃｒｅａｓ Volume: 46 Issue: 5 Pages: 658-664
  • DOI: 10.1097/mpa.0000000000000786
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant